Bisphenol-A promotes antiproliferative effects during neonatal prostate development in male and female gerbils

Conselho Nacional de Desenvolvimento Científico e Tecnol[ogico (CNPq)

Localized matrix metalloproteinase (MMP)-2 and MMP-9 activity in the rat ventral prostate during the first week of postnatal development

The initial events in prostatic morphogenesis involve cell proliferation, epithelial canalization and outgrowth toward the stroma. We have hypothesized that stromal rearrangement takes place at the sites of epithelial growth and branching and that this rearrangement involves the action of gelatinases matrix metalloproteinase (MMP)-2 and MMP-9. Thus, the purpose of the present study was to characterize structural aspects of epithelial growth during the first week of postnatal development of the rat ventral prostate and to investigate the expression, localization and activity of MMP-2 and MMP-9 during this period by histological, ultrastructural and immunocytochemical analysis, in addition to gel zymography, in situ zymography and Western blotting. An increasing complexity of prostatic architeture was observed within the first postnatal week. Concurrently, the stroma became more organized and some cells differentiated into smooth muscle cells. Reticulin fibers appeared in a basket-like arrangement around both growing tips and epithelial sprouts, associated with a fainter staining for laminin. MMP-2 and MMP-9 activities were detected. MMP-2/MMP-9 expression decreased during the first week. Developing epithelial cords showed strong and difuse gelatinolytic activity. This activity coincided with the distribution of MMP-2 as determined by immunocytochemistry. on the other hand, MMP-9 was rather concentrated at the epithelial tips. These results suggest that gelatinolytic activity (with contribution of both MMP-2 and MMP-9) in the epithelium and at the epithelium-stroma interface are at least in part responsible for the tissue remodeling that allows epithelial growth and its projection into the surrounding stroma.

Prenatal exposure to testosterone masculinises the female gerbil and promotes the development of lesions in the prostate (Skene

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postnatal growth of the ventral prostate in Wistar rats: A stereological and morphometrical study

Morphological and stereological analyses were used to characterize the growth kinetics of the Wistar rat ventral prostate (VP). Volume density and absolute volume of the epithelium, lumen, smooth muscle cells (SMCs), and nonmuscular stroma were determined by stereology and paired with plasma testosterone levels and different morphometric measurements. The VP shows an initial growth within the first 3 weeks, a resting phase, and the puberal growth. The puberal growth was coincident with the raise in plasma testosterone. Lumen formation occurred within the 3 postnatal weeks. After an expected increase during puberty, the lumen showed a further increase at the 12th week. The volume density of the nonmuscular stroma and of the SMCs decreased slowly postnatally. Absolute volume of the luminal compartment showed three phases of growth (weeks 1-3, 6-9, and 11-12). on the other hand, the increase in the absolute volume of the epithelium was steady up to the 8th week and then showed a marked increase up the 10th week. The increase in epithelial volume was characterized morphologically by the presence of epithelial infoldings and sprouts. The growth of the epithelium showed a 2-week delay as compared to the lumen and occurred only until the 10th week. The epithelial height was variable but could be related to the synthetic activity of the epithelium. In conclusion, the postnatal growth of the VP results from a combination of epithelial proliferation/differentiation and synthesis/accumulation of the secretory products in the lumen.

Lobe identity in the Mongolian gerbil prostatic complex: A new rodent model for prostate study

Knowledge of structural and physiological differences among the prostatic lobes (PL) is the basis for development of experimental studies in traditional laboratory rodents. Although Mongolian gerbil reproductive organs have been increasingly investigated, its prostate structure is far from being properly known, and investigations of this organ focused on the ventral lobe (VL). Thus, the present study provides a thorough morphological description of prostatic complex in the male adult gerbil on the basis of topographic, histological, and ultrastructural analysis and ductal branching. Like other rodents, four pairs of PL were observed. However, in contrast to the rat and mouse, the VL is the least voluminous component and the dorsolateral lobe (DLL) is the most prominent and spatially isolated from remaining PL. The occurrence of a dorsal lobe (DL), hidden between bladder and insertion of seminal vesicles, has not been mentioned in previous reports with Mongolian gerbil. Collagenase digestion followed by microdissection revealed that, except for DL, which has a tubularacinar organization, all PL exhibit tubular organization and variable ductal branching. Distinct histological and ultrastructural features such as secretory epithelium, aspect of luminal secretion and stromal organization are reported for each PL and are confirmed by morphometric and stereological methods. Histological sections showed at least three intralobar segments in VL and DL. Ultrastructural analysis evidenced that, although luminal epithelial cells of PL share typical features of exocrine secretory cells, there are striking lobe phenotypical variations. Both merocrine and apocrine pathways are observed in variable rates in all PL, with the predominance of the former in the DLL and the latter in the CG. The morphological observations presented herein point to distinct structural identities for each PL, which probably reflects,specific functional compromise of seminal fluid secretion. These data also point to the gerbil as a good model for investigations concerning the regulation of prostate development and homeostasis, mainly with regard to the dorsal and dorsolateral PL.

Implications of intrauterine protein malnutrition on prostate growth, maturation and aging

Aims Maternal malnutrition by low protein diet is associated with an increased incidence of metabolic disorders and decreased male fertility in adult life. This study aimed to assess the impact of maternal protein malnutrition (MPM) on prostate growth, tissue organization and lesion incidence with aging. Main methods Wistar rat dams were distributed into two groups, which were control (NP; fed a normal diet containing 17% protein) or a restricted protein diet (RP, fed a diet containing 6% protein) during gestation. After delivery all mothers and offspring received a normal diet. Biometrical parameters, hormonal levels and prostates were harvested at post-natal days (PND) 30, 120 and 360. Key findings MPM promoted low birth weight, decreased ano-genital distance (AGD) and reduced androgen plasma levels of male pups. Prostatic lobes from RP groups presented reduced glandular weight, epithelial cell height and alveolar diameter. The epithelial cell proliferation and collagen deposition were increased in RP group. Incidences of epithelial dysplasia and prostatitis were higher in the RP offspring than in the NP offspring at PND360. Significance Our findings show that MPM delays prostate development, growth and maturation until adulthood, probably as a result of low testosterone stimuli. The higher incidence of cellular dysplasia and prostatitis suggests that MPM increases prostate susceptibility to diseases with aging. © 2013 Elsevier Inc.

Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood

Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 μg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (∼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.

Intrauterine exposure to bisphenol A promotes different effects in both neonatal and adult prostate of male and female gerbils (Meriones unguiculatus)

Substances that mimic endogenous hormones may alter the cell signaling that govern prostate development and predispose it to developing lesions in adult and senile life. Bisphenol A is able to mimic estrogens, and studies have demonstrated that low levels of exposure to this compound have caused alterations during prostate development. The aim of this study was to describe the prostate development in both male and female neonatal gerbils in normal conditions and under exposure to BPA during intrauterine life, and also to analyze whether the effects of intrauterine exposure to BPA remain in adulthood. Morphological, stereological, three-dimensional reconstruction, and immunohistochemical methods were employed. The results demonstrated that in 1-day-old normal gerbils, the female paraurethral glands and the male ventral lobe are morphologically similar, although its tissue components-epithelial buds (EB), periurethral mesenchyme (PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth muscle (SM)-have presented different immunolabeling pattern for androgen receptor (AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a differential response of male and female prostate to intrauterine BPA exposure. In 1-day-old males, the intrauterine exposure to BPA caused a decrease of AR-positive cells in the PeM and SM, and a decrease of the proliferative status in the EB. In contrast, no morphological alterations were observed in ventral prostate of adult males. In 1-day-old females, BPA exposure promoted an increase of estrogen receptor alpha (ERα) positive cells in PeM and PaM, a decrease of AR-positive cells in EB and PeM, besides a reduction of cell proliferation in EB. Additionally, the adult female prostate of BPA-exposed animals presented an increase of AR- and PCNA-positive cells. These results suggest that the prostate of female gerbils were more susceptible to the intrauterine BPA effects, since they became more proliferative in adult life. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Early Changes Induced by Short-Term Low-Dose Cadmium Exposure in Rat Ventral and Dorsolateral Prostates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exposição in utero ao desregulador endocrino bisfenol A e ao agente quimiopreventivo indol-3-carbinol: efeitos sobra a morfogênese e a suscetibilidade à carcinogênese prostática

Pós-graduação em Biologia Geral e Aplicada - IBB

Programaçao fetal por restrição proteica in utero: avaliação do imprinting estrogênico nas próstatas ventral e dorsolateral do rato Wistar

Pós-graduação em Biologia Geral e Aplicada - IBB

Exposição crônica ao cádmio e/ou à cafeína: alterações estruturais, ultraestruturais e bioquímicas na próstata do rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Papel do resveratrol sobra a modulação do receptor Aril-hidrocarboneto (AhR) e o desenvolvimento da próstata de ratos expostos ao 2, 3, 7, 8-tetraclorodibenzo-p-dioxina (TDCC) durante a gestação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)